Related Experiment Video
Updated: Sep 21, 2025
08:00
Sample Preparation and Relative Quantitation using Reductive Methylation of Amines for Peptidomics Studies
Published on: November 4, 2021
2.4K
Reductive aminations by imine reductases: from milligrams to tons.
Amelia K Gilio1, Thomas W Thorpe2, Nicholas Turner2
1Department of Chemistry, University of York Heslington York YO10 5DD UK gideon.grogan@york.ac.uk.
Chemical Science
|June 3, 2022
Summary
Imine reductase (IRED) enzymes enable sustainable, selective synthesis of chiral amines via asymmetric reductive amination. This biocatalytic approach has advanced from lab-scale to industrial ton-scale production of valuable amine compounds.
Area of Science:
- Biocatalysis
- Synthetic Organic Chemistry
- Enzyme Engineering
Background:
- Reductive amination of carbonyl compounds is crucial for synthesizing amines.
- Chiral amines are vital building blocks for pharmaceuticals and bioactive molecules.
- Traditional methods rely on transition metal catalysis, but biocatalysis offers enhanced selectivity and sustainability.
Purpose of the Study:
- To provide a perspective on the development of imine reductase (IRED)-catalyzed asymmetric reductive amination.
- To highlight the transition from laboratory-scale discovery to industrial-scale application.
- To discuss the role of enzyme engineering in optimizing IRED catalysts.
Main Methods:
- Surveying synthetic chemistry applications of IREDs.
- Analyzing structure-based and protein engineering approaches.
- Reviewing industrial case studies of IRED-catalyzed reactions.
Main Results:
- Biocatalytic asymmetric reductive amination using IREDs has been successfully scaled to ton-scale production.
- Protein engineering has significantly improved IREDs' activity, selectivity, and stability.
- A diverse range of chiral amines can now be synthesized efficiently using IRED technology.
Conclusions:
- IRED-catalyzed reductive amination represents a powerful and sustainable industrial strategy for chiral amine synthesis.
- Continued advancements in enzyme engineering will further expand the scope and efficiency of biocatalytic amine production.
- This technology offers a greener alternative to traditional chemical catalysis for producing essential chiral amine intermediates.
More Related Videos
Related Concept Videos
01:38Preparation of Amines: Reductive Amination of Aldehydes and Ketones
3.2K
Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.
3.2K
01:20Amides to Amines: LiAlH4 Reduction
5.1K
Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
5.1K
00:55Nitriles to Amines: LiAlH4 Reduction
3.8K
Nitriles are reduced to amines in the presence of strong reducing agents like lithium aluminum hydride through a typical nucleophilic acyl substitution. The reaction requires two equivalents of the reducing agent. The reducing agent acts as a source of hydride ions.
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...
3.8K
01:29Preparation of Amines: Reduction of Oximes and Nitro Compounds
4.1K
Oximes can be reduced to primary amines using catalytic hydrogenation, hydride reduction, or sodium metal reduction. The reduction of aliphatic and aromatic nitro compounds to primary amines takes place by either catalytic hydrogenation or by using active metals like Fe, Zn, and Sn in the presence of an acid.
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
4.1K
01:13Preparation of Amines: Reduction of Amides and Nitriles
2.6K
Nitriles can be reduced to primary amines using reducing agents like lithium aluminum hydride or catalytic hydrogenation. The reduction introduces an amino group with an extra carbon in the skeleton. Nitriles are formed from the reaction between alkyl halides and sodium cyanide through the SN2 mechanism. Primary alkyl halides are the preferred substrates to prepare nitriles.
Amides can be reduced to primary, secondary, and tertiary amines using catalytic hydrogenation, active metals like Fe,...
Amides can be reduced to primary, secondary, and tertiary amines using catalytic hydrogenation, active metals like Fe,...
2.6K
01:23Aldehydes and Ketones with Amines: Imine Formation Mechanism
6.5K
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
6.5K